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IPD-MHC Database

Introduction to the Salmonid MHC

 

Nomenclature of salmonid MHC loci

Salmonid MHC locus nomenclature follows guidelines by Klein et al. (1). The first letter corresponds to the respective MHC class I lineage (S, U, Z and L in salmonid fish), or D (duo) for class II; The second letter designates the locus (starting from A); The third letter specifies A for class IA, or A or B for class IIA or IIB, respectively. Corresponding loci in different salmonid species are given a similar name.  Differences in gene copy numbers between individuals and species occasionally requires the usage of additional locus numbers (e.g., UCA1 and UCA2). The non-classical gene SAA was previously named UAA (2) but currently the name UAA is not in use. The salmonid Z sequences were previously designated ZE (3). Sequence differences between salmonid MHC class I lineages were analyzed in detail by Dijkstra et al. (4). The study by Harstad et al. (5) describes both classical as well as non-classical salmonid MHC class II loci. For a comprehensive assessment of salmonid MHC class I and II loci that utilize the current nomenclature please see the study by Lukacs et al. (6).

 

Salmonid fish possess a single classical MHC class I locus, UBA, displaying unprecedented allelic divergence

There is only one classical MHC class I locus in rainbow trout and Atlantic salmon, which is designated UBA. An Atlantic salmon UBA sequence was the first classical MHC class I sequence ever reported for teleost fish (7). Large differences between salmonid classical MHC class I sequences were observed soon after (8, 9), but a lot of additional work was required to show that these levels of high divergence included true alleles (10, 11). A study by Kiryu et al. (12) describes the currently known range of divergence for salmonid UBA alleles. Allelic divergence in the a1 and a2 domains is unprecedented (with up to 70% and 50% differences in amino acid residues, respectively), and even in the a3, transmembrane, and cytoplasmic regions considerable allelic variation is found. Furthermore, UBA polymorphism is characterized by mosaic similarity patterns indicating interallelic recombination events that map to the intron between the a1 and a2 encoding exons (10); such recombination is stimulated by the large size (>10 kb) of this intron (13).

 

Salmonid fishes presumably  have a single classical MHC class II locus, with the IIA gene (DAA) showing a similar degree of polymorphism as the IIB gene (DAB)

After initial discovery of salmonid classical MHC IIa and IIb genes (14, 15), it was found that the level of salmonid MHC class IIb polymorphism parallels that of humans (10).  More recently it was found that salmonid MHC class IIa also displays a high degree of polymorphism, similar to that of salmonid MHC class IIb, which is much higher than is commonly found for mammalian MHC class IIa (16). Despite attempts by several research groups, the salmonid MHC class II locus has been resilient to cloning. However, available evidence indicates that there is only a single classical MHC class II locus with closely linked DAA and DBA (17, 18).

 

References:

  1. Klein J, Bontrop RE, Dawkins RL, et al.
    Nomenclature for the major histocompatibility complexes of different species: a proposal.
    Immunogenetics. 1990;31:217-9.
  2. Shum BP, Rajalingam R, Magor KE, et al.
    A divergent non-classical class I gene conserved in salmonids.
    Immunogenetics. 1999;49:479-90.
  3. Kruiswijk CP, Hermsen TT, Westphal AH, Savelkoul HF, Stet RJ.
    A novel functional class I lineage in zebrafish (Danio rerio), carp (Cyprinus carpio), and large barbus (Barbus intermedius) showing an unusual conservation of the peptide binding domains.
    Journal of immunology. 2002;169:1936-47.
  4. Dijkstra JM, Katagiri T, Hosomichi K, et al.
    A third broad lineage of major histocompatibility complex (MHC) class I in teleost fish; MHC class II linkage and processed genes.
    Immunogenetics. 2007;59:305-21.
  5. Harstad H, Lukacs MF, Bakke HG, Grimholt U.
    Multiple expressed MHC class II loci in salmonids; details of one non-classical region in Atlantic salmon (Salmo salar).
    BMC Genomics. 2008;9:193.
  6. Lukacs MF, Harstad H, Bakke HG, et al.
    Comprehensive analysis of MHC class I genes from the U-, S-, and Z-lineages in Atlantic salmon.
    BMC Genomics. 2010;11:154.
  7. Grimholt U, Hordvik I, Fosse VM, Olsaker I, Endresen C, Lie O.
    Molecular cloning of major histocompatibility complex class I cDNAs from Atlantic salmon (Salmo salar).
    Immunogenetics. 1993;37:469-73.
  8. Hansen JD, Strassburger P, Du Pasquier L.
    Conservation of an alpha 2 domain within the teleostean world, MHC class I from the rainbow trout Oncorhynchus mykiss.
    Developmental and comparative immunology. 1996;20:417-25.
  9. Miller KM, Withler RE.
    Mhc diversity in Pacific salmon: population structure and trans-species allelism.
    Hereditas. 1997;127:83-95.
  10. Shum BP, Guethlein L, Flodin LR, et al.
    Modes of salmonid MHC class I and II evolution differ from the primate paradigm.
    Journal of immunology. 2001;166:3297-308.
  11. Aoyagi K, Dijkstra JM, Xia C, et al.
    Classical MHC class I genes composed of highly divergent sequence lineages share a single locus in rainbow trout (Oncorhynchus mykiss).
    Journal of immunology. 2002;168:260-73.
  12. Kiryu I, Dijkstra JM, Sarder RI, Fujiwara A, Yoshiura Y, Ototake M.
    New MHC class Ia domain lineages in rainbow trout (Oncorhynchus mykiss) which are shared with other fish species.
    Fish & shellfish immunology. 2005;18:243-54.
  13. Shiina T, Dijkstra JM, Shimizu S, et al.
    Interchromosomal duplication of major histocompatibility complex class I regions in rainbow trout (Oncorhynchus mykiss), a species with a presumably recent tetraploid ancestry.
    Immunogenetics. 2005;56:878-93.
  14. Hordvik I, Grimholt U, Fosse VM, Lie O, Endresen C.
    Cloning and sequence analysis of cDNAs encoding the MHC class II beta chain in Atlantic salmon (Salmo salar).
    Immunogenetics. 1993;37:437-41.
  15. Grimholt U, Getahun A, Hermsen T, Stet RJ.
    The major histocompatibility class II alpha chain in salmonid fishes.
    Developmental and comparative immunology. 2000;24:751-63./li>
  16. Gomez D, Conejeros P, Marshall SH, Consuegra S.
    MHC evolution in three salmonid species: a comparison between class II alpha and beta genes.
    Immunogenetics. 2010;62:531-42.
  17. Stet RJ, de Vries B, Mudde K, et al.
    Unique haplotypes of co-segregating major histocompatibility class II A and class II B alleles in Atlantic salmon (Salmo salar) give rise to diverse class II genotypes.
    Immunogenetics. 2002;54:320-31.
  18. Phillips RB, Zimmerman A, Noakes MA, et al.
    Physical and genetic mapping of the rainbow trout major histocompatibility regions: evidence for duplication of the class I region.
    Immunogenetics. 2003;55:561-9.

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